Tankyrase1(TNKS1)plays an essential role in cancer progression by regulating telomere length.The study aimed to determine expression of TNKS1 and its regulation in colorectal cancer(CRC)in 20 samples from Saudi patien...Tankyrase1(TNKS1)plays an essential role in cancer progression by regulating telomere length.The study aimed to determine expression of TNKS1 and its regulation in colorectal cancer(CRC)in 20 samples from Saudi patients.mRNA expression of TNKS1 in CRC and paired normal tissues was measured by qRT-PCR.Epigenetic modification of TNKS1 promoter was determined by methylation-specific PCR while somatic mutation was analyzed by Sanger sequencing in exon 10 of the gene.All cancerous and normal tissues expressed TNKS1,but level of expression in CRC tissues was significantly associated with tumor stage though no other parameters;age,gender,and tumor location,showed any correlation.Expression of TNKS1 was markedly higher in earlier(I,II)than in later(Ⅲ,Ⅳ)stages of CRC development.Both cancerous and healthy tissues had unmethylated promoters.Sanger sequencing of exon 10 masked any somatic mutation in the samples.Our findings suggest that up-regulation of TNKS1 was inversely correlated with cancer progression in CRC,indicating that TNKS1 participates in the initiation of CRC by stabilizing telomere length in the first phase of cancer progression.Mechanisms other than TNKS1 might play a role in malignant tumor progression and telomere maintenance in the late stages of CRC.展开更多
基金funded by King Abdulaziz City for Science and Technology(KACST),grant number(1-17-01-001-0056).
文摘Tankyrase1(TNKS1)plays an essential role in cancer progression by regulating telomere length.The study aimed to determine expression of TNKS1 and its regulation in colorectal cancer(CRC)in 20 samples from Saudi patients.mRNA expression of TNKS1 in CRC and paired normal tissues was measured by qRT-PCR.Epigenetic modification of TNKS1 promoter was determined by methylation-specific PCR while somatic mutation was analyzed by Sanger sequencing in exon 10 of the gene.All cancerous and normal tissues expressed TNKS1,but level of expression in CRC tissues was significantly associated with tumor stage though no other parameters;age,gender,and tumor location,showed any correlation.Expression of TNKS1 was markedly higher in earlier(I,II)than in later(Ⅲ,Ⅳ)stages of CRC development.Both cancerous and healthy tissues had unmethylated promoters.Sanger sequencing of exon 10 masked any somatic mutation in the samples.Our findings suggest that up-regulation of TNKS1 was inversely correlated with cancer progression in CRC,indicating that TNKS1 participates in the initiation of CRC by stabilizing telomere length in the first phase of cancer progression.Mechanisms other than TNKS1 might play a role in malignant tumor progression and telomere maintenance in the late stages of CRC.